Temporal differential effects of post-injury alcohol consumption in a mouse model of blast-induced traumatic brain injury

Abstract

Traumatic brain injury is a prevalent condition that affects millions worldwide with no clear understanding or effective therapeutic management available. Military soldiers have a high risk of exposure to blast-induced traumatic brain injury (bTBI). Furthermore, alcohol drinking is common in this population, and studies have shown that post-TBI alcohol exposure can result in memory loss. Hence, it is possible that alcohol could contribute to the overall pathological outcome of brain trauma. However, such a possibility has not been explored in detail. Here, we combined a mild bTBI (mbTBI) model with the drinking-in-the-dark (DID) paradigm to investigate the pathological synergy between mbTBI and alcohol consumption by examining brain oxidative stress levels and behavioral alterations in mice. The results revealed the anxiolytic and short-term memory improvement effects of post-trauma alcohol drinking examined at an early timepoint post mbTBI. However, extended alcohol drinking for up to three weeks post mbTBI impaired long-term memory and was accompanied by intensified oxidative stress in brain regions associated with memory and anxiety. These findings, as well as those from previous in vitro TBI/alcohol studies, suggest a pathological synergy of physical force and post-impact alcohol exposure. This knowledge could potentially aid in establishing guidelines for TBI victims to avoid further injury to their brains as well as to help maximize their recovery following TBI.